This article is from WeChat public account: Global Academic Aid (Global_Academia) , the original title:” Finally! “Scientists pry at this hard bone for cancer treatment”, picture from: worm
Cancer is one of the leading causes of death worldwide, killing countless lives every year. In the treatment of cancer, although humans have made a series of breakthroughs, there are still many hard bones. A paper published in the leading journal Science on January 3 provided a new combination therapy. It could bring new breakthroughs in cancer treatment!
Difficult bones
We know that cancer can be simply divided into two categories: one is blood cancer, and leukemia and lymphoma belong to this type of cancer; the other is called “solid tumor”, which means that there are actual tumors. What we usually call lung cancer, liver cancer, and gastric cancer are usually solid tumors.
In the treatment of blood cancer, a revolutionary therapy called “CAR-T” was born a few years ago. This therapy is to isolate immune “T” cells from the patient’s body and then install them with a car navigation system called “CAR” through gene editing. The navigator allows immune cells to target cancer cells and attack them. The CAR and T of the “CAR-T” therapy are also derived from this.
▲ Last year, Emily had been cancer-free for 7 years (Photo courtesy of the Emily Whitehead Foundation: emilywhiteheadfoundation.org) p>
In many blood cancer treatments, CAR-T therapy has achieved very good results. The first girl to receive CAR-T therapy was Emily Whitehead (Emily Whitehead) . She had previously died because of leukemia. After participating in the CAR-T therapy clinical trial, she has been cancer-free for 7 years! With the help of immune cells, the little girl’s leukemia has disappeared, which is equivalent to being “cured.”
For many other blood cancer patients, CAR-T therapy can also bring a miracle of life. Currently, the US FDA has approved the launch of two CAR-T therapies, and more CAR-T therapies are expected to come out this year to benefit patients.
However, for solid tumors, the role of CAR-T therapy has been limited. Many scientists point out that this is because solid tumors lack a “navigation address” that immune cells can recognize. If cancer cells cannot be found, they cannot naturally be attacked. And if the navigation address is set too vague, it will make immune cells mistakenly attack other normal tissues and organs. This is a difficult bone to treat cancer.
Signs specific to cancer
In a paper published online today in Science, scientists found such a “navigation address” that belongs to cancer cells only. This address is called CLDN6, and it is a protein expressed on the cell surface that allows cells to stick tightly together. Interestingly, CLDN6They are particularly abundant during embryonic development, but their content decreases sharply after adulthood. Researchers analyzed more than 50 different tissue types from healthy adults and found that CLDN6 is not found inside.
Interestingly, CLDN6 levels are particularly high in ovarian, lung, and uterine cancers. In other words, in adults, if immune cells can be navigated to the position of CLDN6, they can attack the cancer cells behind this address with a high probability.
Navigation instrument for CLDN6 (Picture source: Reference [1])
Researchers do exactly that. They have developed a new CAR-T therapy in which the navigator targets CLDN6. In vitro experiments, scientists have confirmed that the therapy can indeed effectively kill cancer cells with CLDN6. What’s more important is that it doesn’t “go the wrong way” and “strings gates” to cells expressing CLDN3, CLDN4, CLDN9, so it is very specific to cancer cell attacks.
If the CLDN6 “house number” on cancer cells is removed by gene editing, this cell therapy will lose its ability to attack cancer cells. These results also show that it is indeed designed by researchers to launch an attack on cancer cells by looking for CLDN6.
After just 2 weeks of treatment, the tumors (red) of the mice completely subsided (Image source: Reference [1])
In a mouse model with large ovarian cancer tumors, this CAR-T therapy has achieved significant results. After just 2 weeks of treatment, all mouse tumors had completely subsided. In contrast, tumors in the control group continued to grow wildly.
Improving anti-cancer effects
Researchers are not satisfied with the results achieved. Instead, they realized that in the treatment of blood cancer, immune T cells can come in contact with a large number of “doors” expressed on the surface of cancer cells, so they will expand in large numbers. In the treatment of solid tumors, immune T cells do not have much opportunity to come into contact with the “house number”, which will limit their number and thus their efficacy.
To this end, researchers have specially developed an “anti-cancer vaccine”. In this study, scientists packed the information that can make a “house number” (RNA expressing CLDN6) in a type called “lipid Body “into the mouse’s lymphatic system. Sure enough, with the help of this vaccine, immune T cells expanded a lot. This can also be understood as a rapid growth in the army of anti-cancer immune cells.
Mice that received both CAR-T therapy and RNA vaccine (dark red) showed significant improvement in tumor size and survival (picture Source: Reference [1])
As the number of immune cells increases, the anti-cancer effect of this therapy also improves. If only CAR-T therapy is used, then in mice with refractory lung cancer, it can only delay tumor growth. Less than 20 days after treatment, half of the mice died of cancer. Conversely, if CAR-T therapy andFor RNA vaccine, all mice were still alive after 25 days of treatment, and tumor volume decreased.
In summary, this paper published in Science strongly responds to the difficult problem that CAR-T therapy is difficult to treat solid tumors. The researchers pointed out at the end of the paper that this study provides us with a solid foundation for us to better grasp the hard bones of other cancer treatments and bring the gospel to global patients as soon as possible!
Reference:
[1] K. Reinhard et al., (2019), An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors, Science, DOI: 10.1126 / science.aay5967
This article is from WeChat public account: Global Academic Aid (Global_Academia)